Astrocytic degeneration relates to the severity of disease in frontotemporal dementia
Abstract
The main unifying feature of cases with frontotemporal dementia (FTD) is the pattern of brain atrophy. Surprisingly, there are a variety of underlying histopathologies in cases with the clinical features and typical pattern of atrophy characterizing FTD. This suggests that the degenerative mechanism(s) associated with pyramidal cell loss and gliosis in FTD is likely to be similar in the different histopathological forms of the disease. In this study we tested this hypothesis by analysing a common cell death mechanism, apoptosis, in cases of FTD with either Pick's disease (PiD) (n = 9) or frontotemporal lobar degeneration (FTLD) (n = 7) compared with normal controls (n = 10). Tissue sections from previously analysed cases were stained using anti-activated caspase-3 immunohistochemistry, TUNEL, propidium iodide, and cell- and pathology-specific labels. These markers of apoptosis identified both astrocytes and neurons in regions vulnerable to degeneration in all cases of FTD. However, neuronal apoptosis was rare (<2% of neurons), even at early disease stages where there is considerably less frontotemporal atrophy or pyramidal cell loss. This suggests that other cell death mechanisms account for the progressive neuronal loss in FTD. In contrast, astrocytes with beaded processes and other apoptotic features were very frequent in both PiD and FTLD, with the severity of astrocytosis and astrocytic apoptosis correlating with both the degree of neuronal loss and the stage of disease. These findings provide evidence that astrocytic apoptosis occurs as an early event in different histopathological forms of FTD. Furthermore, this astrocytic apoptosis directly relates to the degree of degeneration in FTD, and becomes the overwhelming pathological feature as the disease progresses.
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In early stages of FTD, apoptosis and dystrophy of astrocytes occur in the brain.
“Already at early stages of FTD, apoptosis and dystrophy of astrocytes have been found in the brain [31]”
Strong correlations between CSF and serum levels for NfL have been previously reported.
“We observed strong correlations between CSF and serum levels for NfL, as it has been previously reported [31, 88, 89].”
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- Authors
- Broe, M.
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- Broe, M.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-09-13
- Volume
- 127
- Issue
- 10
- Pages
- 2214-2220
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2124124662
- Cited by
- 106
- References
- 20
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 13 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 7 · 2014: 8 · 2013: 4 · 2012: 5
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- frontotemporal dementia, Pick's disease, frontotemporal lobar degeneration, neuronal apoptosis, astrocyte activation, caspase-3, TUNEL, neuronal loss, disease severity, brain atrophy, gliosis
- MeSH terms
- Aged, Aged, 80 and over, Astrocytes, Atrophy, Brain, Dementia, Female, Gliosis, Humans, Immunohistochemistry, Male, Middle Aged, Neuroglia, Neurons, Propidium, Severity of Illness Index, Biomarkers, Apoptosis, Caspases, In Situ Nick-End Labeling, Pick Disease of the Brain, Caspase 3
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